Psicobiología del estrés prenatal:implicaciones en el eje hipotálamo-hipofisiario-adrenal de los bebés

The womb is the first developmental environment. After developmental psychobiologists started to investigate intrauterine evolution of infant and its long-term impact, they found that prenatal and postnatal development is influenced by mother’s psychological health. Specifically, scientific research evidence indicates that prenatal stress is a possible cause of subsequent psychopathological vulnerability. This vulnerability comes from stress sensitivity and is the basis of many childhood disorders. In the last decade, there are evidences for a fetal origin of stress sensitivity in the context of the fetal programming theory (Entringer et al., 2009, Grant et al., 2009, Gutteling et al., 2004, Huizink et al., 2004, O’Connor et al., 2005). According to fetal programming hypothesis, babies that have been exposed to high levels of prenatal stress would develop elevated HPA axis reactivity and thus increased stress sensitivity in the postnatal period. In the field of animal psychobiology, several studies have shown that prenatal stress could play some role on fetal programming of neurodevelopment and HPA axis (Glover, 2010, Weinstock, 2005, 2008). In human psychobiology, evidences are less clear (Glover, 2010). Although research in this regard has been growing during the last few years, more studies are warranted to investigate the relationship between maternal stress and fetal programming of neurodevelopment and the HPA axis in humans, to confirm the findings which are evident from animal psychobiology...

Brca1 inactivation induces p27Kip1-dependent cell cycle arrest and delayed development in the mouse mammary gland

One common characteristic of breast cancers arising in carriers of the predisposition gene BRCA1 is a loss of expression of the CDK inhibitor p27(Kip1) (p27), suggesting that p27 interacts epistatically with BRCA1. To investigate this relationship, we examined expression of p27 in mice expressing a dominant negative allele of Brca1 (MMTV-trBr) in the mammary gland. While these mice rarely develop tumors, they showed a 50% increase in p27 protein and a delay in mammary gland development associated with reduced proliferation. In contrast, on a p27 heterozygote background, MMTV-trBrca1 mice showed an increase in S phase cells, and normal mammary development. p27 was the only protein in the cyclin cyclin-dependent kinase network to show altered expression, suggesting that it may be a central mediator of cell cycle arrest in response to loss of function of BRCA1. Furthermore, in human mammary epithelial MCF7 cells expressing BRCA1-specific RNAi and in the BRCA1-deficient human tumor cell line HCC1937, p27 is elevated at the mRNA level compared to cells expressing wild-type BRCA1. We hypothesize that disruption of BRCA1 induces an increase in p27 that inhibits proliferation. Accordingly, reduction in p27 expression leads to enhancement of cellular proliferation in the absence of BRCA1.

Differential involvement of rat medial prefrontal cortex dopamine receptors in modulation of hypothalamic-pituitary-adrenal axis responses to different stressors

Recent investigations have implicated the medial prefrontal cortex (mPFC) in modulation of subcortical pathways that contribute to the generation of behavioural, autonomic and endocrine responses to stress. However, little is known of the mechanisms involved. One of the key neurotransmitters involved in mPFC function is dopamine, and we therefore aimed, in this investigation, to examine the role of mPFC dopamine in response to stress in Wistar rats. In this regard, we infused dopamine antagonists SCH23390 or sulpiride into the mPFC via retrodialysis. We then examined changes in numbers of cells expressing the c-fos immediate-early gene protein product, Fos, in subcortical neuronal populations associated with regulation of hypothalamic-pituitary-adrenal (HPA) axis stress responses in response to either of two stressors; systemic injection of interleukin-1beta, or air puff. The D-1 antagonist, SCH23390, and the D-2 antagonist, sulpiride, both attenuated expression of Fos in the medial parvocellular hypothalamic paraventricular nucleus (mpPVN) corticotropin-releasing factor cells at the apex of the HPA axis, as well as in most extra-hypothalamic brain regions examined in response to interleukin-1beta. By contrast, SCH23390 failed to affect Fos expression in response to air puff in any brain region examined, while sulpiride resulted in an attenuation of the air puff-induced response in only the mpPVN and the bed nucleus of the stria terminalis. These results indicate that the mPFC differentially processes the response to different stressors and that the two types of dopamine receptor may have different roles.

Liver fluke-associated and sporadic cholangiocarcinoma: an immunohistochemical study of bile duct, peribiliary gland and tumour cell phenotypes

Aim: To compare cell phenotypes displayed by cholangiocarcinomas and adjacent bile duct lesions in patients from an area endemic in liver-fluke infestation and those with sporadic cholangiocarcinoma. Methods: 65 fluke-associated and 47 sporadic cholangiocarcinomas and 6 normal livers were studied. Serial paraffin-wax sections were stained immunohistochemically with monoclonal antibodies characterising a Brunner or pyloric gland metaplasia cell phenotype (antigens D10 and 1F6), intestinal goblet cells (antigen 17NM), gastric foveolar apomucin (MUC5AC), a gastrointestinal epithelium cytokeratin (CK20) and the p53 protein. Results: 60% of the 112 cholangiocarcinomas expressed antigen D10, 68% MUC5AC, 33% antigen 17NM and 20% CK20; 37% showed overexpression of p53. When present together in a cholangiocarcinoma, cancer cells expressing D10 were distinct from those displaying 17NM or MUC5AC. Many more fluke-associated cholangiocarcinomas than sporadic cholangiocarcinomas displayed 17NM and p53 expression. Most cases of hyperplastic and dysplastic biliary epithelium expressed D10 strongly. Pyloric gland metaplasia and peribiliary glands displayed D10 and 1F6, with peribiliary gland hyperplasia more evident in the livers with fluke-associated cholangiocarcinoma; goblet cells in intestinal metaplasia stained for 17NM. No notable association of expression between any two antigens (including p53) was found in the cancers. Conclusions: Most cases of dysplastic biliary epithelium and cholangiocarcinoma display a Brunner or pyloric gland cell phenotype and a gastric foveolar cell phenotype. The expression of D10 in hyperplastic and dysplastic epithelium and in cholangiocarcinoma is consistent with a dysplasia-carcinoma sequence. Many more fluke-associated cholangiocarcinomas than sporadic cholangiocarcinoma display an intestinal goblet cell phenotype and overexpress p53, indicating differences in the aetiopathology of the cancers in the two groups of patients.

The relationship between alexithymia and salivary cortisol levels in somatoform disorders

The purpose of this study was to investigate cortisol levels as a function of the hypothalamic-pituitary-adrenal axis (HPA) in relation to alexithymia in patients with somatoform disorders (SFD). Diurnal salivary cortisol was sampled in 32 patients with SFD who also underwent a psychiatric examination and filled in questionnaires (Toronto Alexithymia Scale, TAS scale; Screening for Somatoform Symptoms, SOMS scale; Hamilton Depression Scale, HAMD). The mean TAS total score in the sample was 55.69.6, 32% of patients being classified as alexithymic on the basis of their TAS scores. Depression scores were moderate (HAMD=13.2, Beck Depression Inventory, BDI=16.5). The patients' alexithymia scores (TAS scale Difficulty identifying feelings) correlated significantly positively with their somatization scale scores (Symptom Checklist-90 Revised, SCL-90-R); r=0.3438 (P0.05) and their scores on the Global Severity Index (GSI) on the SCL-90-R; r=0.781 (P0.01). Regression analysis was performed with cortisol variables as the dependent variables. Cortisol levels [measured by the area under the curve-ground (AUC-G), area under the curve-increase (AUC-I) and morning cortisol (MCS)] were best predicted in a multiple linear regression model by lower depressive scores (HAMD) and more psychopathological symptoms (SCL-90-R). No significant correlations were found between the patients' alexithymia scores (TAS) and cortisol levels. The healthy control group (n=25) demonstrated significantly higher cortisol levels than did the patients with SFD; in both tests P0.001 for AUC-G and AUC-I. However, the two groups did not differ in terms of their mean morning cortisol levels (P0.05). The results suggest that pre-existing hypocortisolism might possibly be associated with SFD.

Pituitary volume in patients with bipolar disorder and their first-degree relatives

Background: Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been reported in bipolar disorder (BD), but previous magnetic resonance imaging (MRI) studies of pituitary gland volume in BD have yielded inconsistent findings. In addition, the contribution of genetic factors to the pituitary changes in BD remains largely unknown. Method: We used MRI to investigate the pituitary volume in 29 remitted patients with BD, 49 of their first-degree relatives (of whom 15 had a diagnosis of Major Depressive Disorder), and 52 age- and gender-matched healthy controls. Results: BD patients had a significantly larger pituitary volume compared with their relatives and healthy controls. Pituitary volume did not differ between controls and healthy relatives or relatives diagnosed with major depression. Limitations: Direct measures of HPA function (i.e., hormonal levels) were not available. Conclusions: These findings suggest that enlarged pituitary volume is associated with disease expression but not genetic susceptibility to BD. © 2009 Elsevier B.V. All rights reserved.

High Diagnostic Accuracy And Reproducibility Of Fine-needle Aspiration Cytology For Diagnosing Salivary Gland Tumors: Cytohistologic Correlation In 182 Cases.

The purpose of this study was to assess the efficacy and reproducibility of the cytologic diagnosis of salivary gland tumors (SGTs) using fine-needle aspiration cytology (FNAC). The study aimed to determine diagnostic accuracy, sensitivity, and specificity and to evaluate the extent of interobserver agreement. We retrospectively evaluated SGTs from the files of the Division of Pathology at the Clinics Hospital of São Paulo and Piracicaba Dental School between 2000 and 2006. We performed cytohistologic correlation in 182 SGTs. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 94%, 100%, 100%, 100%, and 99%, respectively. The interobserver cytologic reproducibility showed significant statistical concordance (P < .0001). FNAC is an effective tool for performing a reliable preoperative diagnosis in SGTs and shows high diagnostic accuracy and consistent interobserver reproducibility. Further FNAC studies analyzing large samples of malignant SGTs and reactive salivary lesions are needed to confirm their accuracy.

[the Use Of Fish On Buccal Smear To Investigate Mosaicism With A 45,x Cell Line: Study On Healthy Men And Patients With Disorders Of Sex Development].

To verify whether fluorescence in situ hybridization (FISH) of cells from the buccal epithelium could be employed to detect cryptomosaicism with a 45,X lineage in 46,XY patients. Samples of nineteen 46,XY healthy young men and five patients with disorders of sex development (DSD), four 45,X/46,XY and one 46,XY were used. FISH analysis with X and Y specific probes on interphase nuclei from blood lymphocytes and buccal epithelium were analyzed to investigate the proportion of nuclei containing only the signal of the X chromosome. The frequency of nuclei containing only the X signal in the two tissues of healthy men did not differ (p = 0.69). In all patients with DSD this frequency was significantly higher, and there was no difference between the two tissues (p = 0.38), either. Investigation of mosaicism with a 45,X cell line in patients with 46,XY DSD or sterility can be done by FISH directly using cells from the buccal epithelium.

[association Between Physical And Psychosocial Impacts Of Oral Disorders And Quality Of Life Among The Elderly].

This study sought to evaluate the association between the impact of oral disorders in terms of physical/psychosocial dimensions and quality of life among the elderly. It involved a cross-sectional study conducted among the elderly (65-74 years) in 2008/2009. The social impact was assessed using the Oral Health Impact Profile (OHIP 14) and the quality of life using the SF 12 Short-Form Health Survey. Descriptive, univariate and multivariate (logistic regression) analysis was conducted with correction for the design effect, using SPSS(r)18.0 software. Of the 800 individuals approached, 736 elderly individuals participated (TR = 92%), with a mean age of 67.77 years, the majority of whom showed no impact based on the measurement of the prevalence of OHIP. The functional limitation dimension of the OHIP was associated with the physical domain of the SF12, irrespective of the other variables investigated. However, the seriousness of OHIP and its psychological discomfort and disability dimensions was associated with the mental domain of the SF12. The conclusion reached is that some impacts of oral disorders were associated with unsatisfactory quality of life in the physical and mental domains.

Sinonasal Disorders In Hematopoietic Stem Cell Transplantation.

hematopoietic stem cell transplantation (HSCT) is associated with more respiratory infections due to immunosuppression. this study aimed to verify the frequency of rhinosinusitis after HSCT, and the association between rhinosinusitis and chronic graft vs. host disease (GVHD) and type of transplantation, clinical treatment, surgical treatment, and survival. this was a retrospective study in a tertiary university hospital. A total of 95 patients with hematological diseases undergoing HSCT between 1996 and 2011 were selected. chronic myeloid leukemia was the most prevalent disease. The type of transplant most often performed was the allogenic type (85.26%). The frequency of rhinosinusitis was 36%, with no difference between the autologous and the allogenic types. Chronic GVHD occurred in 30% of patients. Patients with GVHD had a higher frequency and recurrence of rhinosinusitis, in addition to more frequent need for endoscopic sinusectomy and decreased overall survival. there was a higher frequency of rhinosinusitis in HSCT and GVHD. The type of transplant does not appear to predispose to the occurrence of rhinosinusitis. GVHD seems to be an aggravating factor and requires a more stringent treatment.

Indole-3-carbinol Attenuates The Deleterious Gestational Effects Of Bisphenol A Exposure On The Prostate Gland Of Male F1 Rats.

Bisphenol A (BPA) is a chemical that has been investigated for it potential to cause prostate diseases. In this study, pregnant Sprague-Dawley rats were treated with 25 or 250 μg/kg BPA from gestational day (GD) 10 to GD21 with or without concurrent indole-3-carbinol (I3C) feeding. I3C is a phytochemical, and it affords chemoprotection against many types of neoplasia. Male F1 rats from different litters were euthanized on post-natal day (PND) 21 and PND180. BPA-treated groups showed a significant increase in histopathological lesions, but I3C feeding reversed many of these changes, mainly at PND180. Maternal I3C feeding increased prostate epithelial apoptosis in the BPA-treated groups and across age groups. Furthermore, I3C induced partial normalization of the prostate histoarchitecture. The results pointed to a protective effect of maternal I3C feeding during pregnancy in the BPA-exposed male offspring, thereby indicating reduction in the harmful effects of gestational BPA imprinting on the prostate.

Tubular Variant Of Basal Cell Adenoma Shares Immunophenotypical Features With Normal Intercalated Ducts And Is Closely Related To Intercalated Duct Lesions Of Salivary Gland.

The morphological criteria for identification of intercalated duct lesions (IDLs) of salivary glands have been defined recently. It has been hypothesised that IDL could be a precursor of basal cell adenoma (BCA). BCAs show a variety of histological patterns, and the tubular variant is the one that presents the strongest resemblance with IDLs. The aim of this study was to analyse the morphological and immunohistochemical profiles of IDLs and BCAs classified into tubular and non-tubular subtypes, to determine whether or not IDL and tubular BCA represent distinct entities. Eight IDLs, nine tubular BCAs and 19 non-tubular BCAs were studied. All tubular BCAs contained IDL-like areas, which represented 20-70% of the tumour. In non-tubular BCA, IDL-like areas were occasional and small (<5%). One patient presented IDLs, tubular BCAs and IDL/tubular BCA combined lesions. Luminal ductal cells of IDLs and tubular BCAs exhibited positivity for CK7, lysozyme, S100 and DOG1. In the non-tubular BCA group, few luminal cells exhibited such an immunoprofile; they were mainly CK14-positive. Basal/myoepithelial cells of IDLs, tubular BCAs and non-tubular BCAs were positive for CK14, calponin, α-SMA and p63; they were more numerous in BCA lesions. IDL, tubular BCA and non-tubular BCA form a continuum of lesions in which IDLs are related closely to tubular BCA. In both, the immunoprofile of luminal and myoepithelial cells recapitulates the normal intercalated duct. The difference between the adenoma-like subset of IDLs and tubular BCA rests mainly on the larger numbers of myoepithelial cells in the latter. Our findings indicate that at least some BCAs can arise via IDLs.

[temporomandibular Disorders In Fibromyalgia Syndrome: A Short-communication.]

Fibromyalgia syndrome (FMS) is a chronic painful syndrome and the coexistence of a painful condition caused by Temporomandibular Disorders (TMD) and FMS has been frequently raised for several studies, however, more likely hypothesis is that a set of FMS characteristics may lead to the onset of TMD symptoms and they are not merely coexisting conditions. Therefore, our aim is presenting a review of literature about the relation between fibromyalgia and the signs and symptoms of temporomandibular disorders. For this purpose, a bibliographic search was performed of the period of 1990-2013, in the Medline, Pubmed, Lilacs and Scielo databases, using the keywords fibromyalgia, temporomandibular disorders and facial pain. Here we present a set of findings in the literature showing that fibromyalgia can lead to TMD symptoms. These studies demonstrated greater involvement of the stomatognathic system in FMS and myogenic disorders of masticatory system are the most commonly found in those patients. FMS appears to have a series of characteristics that constitute predisposing and triggering factors for TMD.